HPV Vaccine Cuts Cervical Abnormalities by 46

MedicalResearch.com
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Editor: Marie Benz, MD
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March 14 2014
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HPV Vaccination and Prevention of Cervical Abnormalities
MedicalResearch.com Interview with:
Dr Julia Brotherton Victorian Cytology Service, Melbourne, Victoria, Australia
Dr Elizabeth Crowe The University of Queensland, School of Population Health, Brisbane, Australia
Prof. David Whiteman Group Leader / Department Coordinator QIMR Berghofer Medical Research Institute
Royal Brisbane Hospital, QLD 4029
• MedicalResearch.com: What are the main findings of the study?
• 1. We conducted a case-control study in which we retrieved the HPV vaccination histories of young Australian women
who were notified to the Pap smear registry with high-grade cervical lesions or with other types of cervical lesions, and
compared them with the vaccination histories of women whose Pap smears showed only normal cytology.
• 2. We found that women with high grade cervical lesions were significantly less likely than women with normal cytology
to have received 3 doses of the quadrivalent HPV vaccine, equivalent to a vaccine effectiveness of 46%.
• 3. The vaccine effectiveness among 15-19 year old women was even higher at 57%. We believe this reflects the fact that
HPV16 causes an even higher proportion of high grade disease in young women due to its higher oncogenicity and shorter
latent period.
• 4. The HPV vaccine had 34% effectiveness against other cervical lesions (i.e. those not proven to be high grade lesions on
histology).
• 5. We also observed that 2 doses of the vaccine were 21% effective in preventing both high grade lesions and other
grade lesions.
MedicalResearch.com: Were any of the findings unexpected?
• 1. Before this study was performed, we did not know whether less than three doses of vaccine would provide any
protection. Our findings that 2 doses conferred 21% protection against both high grade lesions and other lesions are
encouraging, but suggest that three doses are required for best protection using the current dose schedule.
• MedicalResearch.com: What should clinicians and patients take away from your report?
• 1. This report demonstrates the effectiveness of the HPV vaccine in the ‘real world’ population setting (i.e. outside of
clinical trials).
• 2. The vaccine is targeted against two HPV types (16 and 18) that are known to cause about 50% of high grade cervical
lesions. Among women receiving the vaccine, we observed a 46% reduction in the risk of high grade lesions, consistent with
the vaccine preventing almost all high grade lesions that are caused by HPV 16 and 18.
• 3. Importantly, because the vaccine does not target other HPV types known to cause the remainder of high grade lesions,
it is essential that women continue to be screened, even if they have received the vaccine.
Read the rest of the interview on MedicalResearch.com

HPV Vaccination and Prevention of Cervical Abnormalities
Dr Julia Brotherton Victorian Cytology Service, Melbourne, Victoria, Australia
Dr Elizabeth Crowe The University of Queensland, School of Population Health, Brisbane, Australia
Prof. David Whiteman Group Leader / Department Coordinator QIMR Berghofer Medical Research Institute
Royal Brisbane Hospital, QLD 4029
• MedicalResearch.com: What recommendations do you have for future research as a result
of this study?
• 1. We need to continue to monitor trends in HPV vaccination rates, and also closely
monitor trends in cervical lesions and cancers into the future as it is predicted that vaccine
effectiveness will be seen to improve with longer follow-up times.
• 2. The performance of the Pap smear programs must be monitored to rapidly flag any
changes in screening practices among women.
• 3. While we estimated the effectiveness of 2 doses of the vaccine as 21%, this needs to be
confirmed in other studies.
• Citation:
• Effectiveness of a quadrivalent human papillomavirus vaccine for the prevention of cervical
abnormalitites
MJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g1458 (Published 4 March 2014)
• Cite this as: BMJ 2014;348:g1458

Atrial Fibrillation, Warfarin and Kidney Function after Heart Attack
Juan Jesus Carrero PhD (Pharm and Med)
Associate Professor in Renal Medicine
Karolinska Institutet, Sweden.
• MedicalResearch.com: Why did you choose to study this particular question?
• Answer: We chose this question because there is currently an important knowledge gap regarding safety and effectiveness of common drugs in
individuals with chronic kidney disease. Because kidney dysfunction interferes with drug metabolism and drug elimination, patients with kidney
dysfunction have traditionally been excluded from randomized controlled trials. Yet, practice guidelines are afterwards extrapolated to those in the
absence of formal evaluation.
• MedicalResearch.com: Tell us about your study…. What did you set out to discover?
• Answer: We studied outcomes associated to warfarin treatment in patients with both atrial fibrillation and kidney disease. These individuals are at a
markedly increased risk of bleeding and ischemic stroke. Although such patients have a clear indication for anticoagulant therapy, recent
observational studies in advanced chronic kidney disease have provided conflicting results, suggesting that warfarin treatment may instead confer
harm.
• Our study considered all consecutive Swedish patients with Atrial Fibrillation admitted to the hospital for an acute myocardial infarction. Because of
availability of creatinine assessments, we were able to estimate the severity of underlying chronic kidney disease. Our pre-specified outcomes were
the composite of death, myocardial infarction and stroke, as well as the risk of bleeding, within one year from discharge date.
• MedicalResearch.com: What were your findings?
• Answer: We observed that more than 50% of the included patients were considered to have chronic kidney disease, evidencing the commonness of
kidney dysfunction in individuals with cardiovascular disease.
• Our main finding was that warfarin treatment was associated with a lower risk for the composite outcome without increased risk of bleeding. This
was observed not only for individuals with normal kidney function but also for those with moderate, severe or end-stage kidney disease.
• MedicalResearch.com: What are the implications of the study findings?
• Answer: Our study may therefore suggest that patients with Atrial Fibrillation and renal disease not requiring dialysis can also benefit from warfarin
therapy and thus should not be excluded from this treatment option.
• MedicalResearch.com: What additional research is needed?
• Answer: This study includes individuals with kidney disease not requiring dialysis. The evaluation of warfarin safety in dialysis patients still is not fully
established. Finally, because ours is an observational study, further clinical trials are necessary to definitely answer this question.
• Citation:
• Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation
• Juan Jesús Carrero PhD(Pharm and Med), Marie Evans MD, PhD, Karolina Szummer MD, PhD, Jonas Spaak MD, PhD, Lars Lindhagen PhD, Robert
Edfors MD, Peter Stenvinkel MD, PhD, Stefan H Jacobson MD, PhD, Tomas Jernberg MD, PhD
• JAMA. 2014;311(9):919-928. doi:10.1001/jama.2014.1334

Hepatitis C: About 1% US Population Infected
Scott D. Holmberg, MD, MPH
Chief, Epidemiology and Surveillance Branch
Division of Viral Hepatitis.
• Dr. Holmberg: Based on interview and testing of over 30, 000 National Health and Nutrition and Examination Survey
(NHANES) participants from 2003 to 2010, 273 US residents or about 1%, are chronically (actively) infected with hepatitis C
virus (HCV). This translates to about 2.7 million chronic HCV-infected persons in the non-institutionalized population.
• MedicalResearch.com: Were any of the findings unexpected?
• Dr. Holmberg: This analysis indicated that the number of chronically infected persons are about 500,000 fewer than a similar
NHANES analysis done between 1999 and 2002. This may be related to statistical variation between the two samples, or, as
we have observed, increasing mortality in HCV-infected patients.
• Dr. Holmberg: Hepatitis C virus is a widely prevalent infection that causes more morbidity and mortality than most other
infectious diseases. Because of the long incubation period between infection and overt disease—often 20, 30, or more
years—infected patients and even clinicians may be inclined to dismiss HCV as an indolent, even benign infection. This study
underscores the importance of CDC and US Preventive Services Task Force recommendations that all persons born between
1945 and 1965, about 75% of all cases, should get tested at least once for hepatitis C virus.
• MedicalResearch.com: What recommendations do you have for future research as a result of this study?
• Dr. Holmberg: This analysis needs to be repeated in future years as an important index and measure of trends in chronic
hepatitis C.
• Citation:
• Chronic Hepatitis C Virus Infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010
• Ann Intern Med. 2014;160(5):293-300-300. doi:10.7326/M13-1133
• Maxine M. Denniston, MSPH; Ruth B. Jiles, PhD, MS, MPH; Jan Drobeniuc, MD, PhD; R. Monina Klevens, DDS, MPH; John W.
Ward, MD; Geraldine M. McQuillan, PhD; and Scott D. Holmberg, MD, MPH

Herbal Cannabis Not Proven Effective For Rheumatic Diseases
Mary-Ann Fitzcharles, MB, ChB, MRCP(UK), FRCP(C)
McGill University Health Centre
Division of Rheumatology and Alan Edwards Pain Management Unit
• MedicalResearch.com: What are the highlights of your review?
• Dr. Fitzcharles: Thank you for your interest in the review article which will shortly be published in
Arthritis Care & Research. This was not a research study but rather a review focused towards the
use of herbal cannabis for patients with rheumatic diseases.
• The essence of our message after a thorough review of the literature is that there is not a single
study published regarding efficacy or side effects of herbal cannabis in the rheumatic diseases. It is
notable that almost 2 thirds of persons using herbal cannabis for therapeutic reasons report use for
musculoskeletal complaints. In the 21st century, we cannot rely upon heresay or anecdote to justify
use of a treatment intervention. It is unacceptable to recommend use of a substance without
knowledge of concentration of molecules in the product, any knowledge of blood concentrations
that might have a positive or negative effect, and formal study in defined patient populations with
acceptable endpoint criteria and evidence for short and long term risks.
• With the knowledge of short and long term risks that are emerging from study of recreational user,
we recommend that the herbal product should only be used in the extreme and very rare situation
when a patient with rheumatic disease is suffering severe pain that has been unresponsive to trials
of standard medical therapy.
• Citation:
• The Dilemma of Medical Marijuana Use by Rheumatology Patients
• Mary-Ann Fitzcharles, Daniel J. Clauw, Peter A. Ste-Marie and Yoram Shir
Arthritis Care and Research
Accepted manuscript online: 3 MAR 2014 07:30AM EST | DOI: 10.1002/acr.22267

Obesity Rates Triple in Canada Over 25 Years
Dr. Laurie K. Twells, PhD
School of Pharmacy, Memorial University, St. John’s
Faculty of Medicine, Memorial University
St. John’s Newfoundland and Labrador
• Dr. Twells: Obesity rates in Canada tripled between 1985 and 2011. Although class I obesity (BMI ≥ 30) appears to have
increased at a slower rate, obese classes II (BMI ≥ 35) and III (BMI ≥40) continued to increase disproportionately. Over the
last decade, every province in Canada experienced increases in obesity rates. Overall obesity rates were lower in the west
and higher in the eastern provinces and people over age 40 years were more likely to be overweight/obese than younger
people. By 2019 it is projected that twenty-one per cent of Canadians will be obese but this will vary by province from 15.7%
in British Columbia to 34.6% in Newfoundland and Labrador.
• Dr. Twells: The provincial comparisons in Canada were interesting and presenting the data in this format uncovered the
differences in obesity rates (current and predicted) across the country. The predicted prevalence rates for some provinces
are very concerning given the health system burden and impact on quality of life associated with being in the excessive
weight categories.
• Dr. Twells: In Canada, the number of individuals with a BMI greater than 35 and 40 are predicted to increase over the next
five years. These individuals are at a much higher risk of developing serious comorbid conditions such as hypertension,
dyslipidemia, diabetes, reporting impaired quality of life and dying prematurely. Clinicians will need to be resourced to
manage and treat affected individuals effectively.
• Dr. Twells: One area for future research is the need to help explain why such significant inter-provincial variations exist in
Canada. This might include a focus on evaluating existing provincial policies, programs and approaches to the prevention,
management and treatment of obesity. For example, provincial variation exists in the provision of bariatric surgery, the
training or lack of training of health professionals in weight management and in patient access to other types of expertise in
weight loss such as dieticians and psychologists. There is the potential in Canada for provinces to share effective practices to
improve the overall health of the country.
• Citation:
• Current and predicted prevalence of obesity in Canada: a trend analysis
• Laurie K. Twells PhD, Deborah M. Gregory PhD, Jacinta Reddigan MSc, William K. Midodzi PhD
cmajo 2:E18-E26; published online March 3, 2014, doi:10.9778/cmajo.20130016

Hospital Mortality: Association With Nurses’ Work Load and Education
MedicalResearch.com Interview with: Professor Linda H Aiken PhD, FAAN, FRCN, RN
Claire M. Fagin Leadership Professor in Nursing, Professor of Sociology
Director of the Center for Health Outcomes and Policy Research Center for Health Outcomes and Policy Research
University of Pennsylvania School of Nursing
• MedicalResearch.com: Austerity measures and health-system redesign to minimise hospital expenditures
risk adversely affecting patient outcomes. Against that backdrop, can you start by letting us know the
background of the study?
• Prof. Aiken: European Surgical Outcomes Study in 28 countries showed higher than necessary deaths
after surgery.
• A comparable study in the US showed that despite the nation spending hundreds of millions of dollars on
improving patient safety, there were no improvements in adverse outcomes after surgery in US hospitals
between 2000 and 2009. Clearly it is time to consider new solutions to improving hospital care for surgical
patients, who make up a large proportion of all hospital admissions. Our study was designed to determine
whether there are risks for patients of reducing hospital nurse staffing, and what, if any, are the benefits to
patients of moving to a more educated nurse workforce.
• MedicalResearch.com: Could you tell us a little about what the average workload of nurses were in the
countries you studied is?
• Prof. Aiken: The average patient to nurse ratio in hospitals in the 9 countries is 8.3 patients per nurse
(which compares to about 5.5 in the USA) but these ratios varied from hospitals in which nurses care for 3
patients each to others where nurses care for 18 patients each. On average nurses’ workloads are lowest
in Norway and highest in Spain but within every country there is substantial variation in hospital nurse
staffing. In England with a national health service where standardization might be expected, the
workloads of nurses in some hospitals were double those of others, ranging from 5 patients per nurse to
over 11 patients per nurse. It is this difference in nurse staffing levels across hospitals within every
country that contributes to what we found to be a 7-fold difference in death rates after surgery for similar
kinds of patients. We found every one patient increase in a nurses work load was associated with a 7%
increase in the risk of death for patients– which illustrates the hazards of increasing nurses’ workloads in
attempts to save money. These findings in Europe mirror the findings of papers we have published on
nurses and mortality in the USA.

Hospital Mortality: Association With Nurses’ Work Load and Education
MedicalResearch.com Interview with: Professor Linda H Aiken PhD, FAAN, FRCN, RN
Claire M. Fagin Leadership Professor in Nursing, Professor of Sociology
Director of the Center for Health Outcomes and Policy Research Center for Health Outcomes and Policy Research
University of Pennsylvania School of Nursing
• MedicalResearch.com: Can you tell us a little more about your findings with regard to nurses’ education?
• Prof. Aiken: Generally we think of educational attainment as a characteristic of an individual. But the educational composition of a hospital’s nursing staff is also an
attribute of an institution. In Norway and Spain, all nurses must have a bachelor’s degree but in other countries, hospitals may employ nurses with and without
university education. There has been a contentious debate within the European Union on standardization of nursing education, and whether the goal of
standardization should be the bachelor’s degree as in other professions. Currently two very different levels of education for nurses are recognized within the
EU: nurses with 12 years of general schooling plus university education and nurses with only 10 years of general schooling followed by vocational training. Like nurse
staffing, the educational composition of nurses in hospitals varies substantially with some hospitals having no nurses with bachelor’s qualifications and some
hospitals having 100% bachelor’s qualified nurses. In England, for example, the NHS hospitals studied varied from 10% of bachelor’s educated nurses to 49%. That
hospital-level variation in the proportion of nurses with bachelor’s education was significantly associated with patient deaths, after taking into account other possible
explanations including nurses’ workloads and how sick the patients were before surgery. We found that every 10% increase in the proportion of nurses in a hospital
with bachelor’s qualifications was associated with a 7% decline in patient deaths. The Institute of Medicine of the National Academy of Sciences has acted upon our
similar findings in the USA and has proposed that by 2020, at least 80% of USA nurses should hold the bachelor’s degree in nursing.
• MedicalResearch.com: Were there any unusual findings you’d like to comment on?
• Prof. Aiken: Patients have the highest risk of death after surgery in hospitals where nurses with lower education care for more patients each.
• Our most important finding for policymakers and consumers is that there is an unjustifiable difference in death rates following common surgery across hospitals in
every country, and differences in nursing resources are a contributing factor to high death rates in many hospitals.
• In every country there are well performing hospitals suggesting that even under less than optimal economic circumstances it is possible to achieve a high quality of
hospital care. A reasonable strategy to proceed in reducing preventable hospital deaths would appear to be improving nurse staffing in the hospitals in every country
where nurses’ workloads are high, and transitioning to bachelor’s education for nurses.
• Some might say that university education for nurses is not feasible for a variety of reasons. The fact that both Norway, a well-resourced country, and Spain, a country
struggling more to contain spending, could have successfully transitioned to an all university educated nurse workforce suggests that all countries in Europe could
make the transition, and our results suggest that such a transition is in the public interest.
• MedicalResearch.com: What conclusions can be drawn from your results, and what are the implications for the future?
• Prof. Aiken: While our study was immensely complicated to conduct, the conclusions and recommendations are remarkably simple. Modern hospitals exist to
provide 24 hour professional nursing care to people too sick to recover at home. Thus it is foolish at best, and fatal at worst to under invest in nursing which is the
primary service provided by hospitals. Health reform initiatives and austerity measures, both of which tend to focus on reducing hospital nurses, put patients at
serious risk of unnecessary death and other adverse outcomes.
• Given the aging of Europe (and the USA), more nurses will be needed in the future. It is unrealistic to expect the best and brightest of next generations to enter
careers that do not provide a university education. There won’t be enough talented and committed professional nurses to take on impossible burdens of
unreasonable workloads and unsafe patient care. Improving quality of hospital care now and for the future requires serious investments in professional nurses.
• Citation:
• Aiken LH, Sloane DM, Bruyneel L, Van den Heede K, Griffiths P, Busse R, Diomidous M, Kinnunen J, Kozka M, Lesaffre E, McHugh M, Moreno-Casbas MT, Rafferty AM,
Schwendimann R, Tishelman C, van Achterberg T, Sermeus W. 2014. Association of nurse staffing and education with hospital mortality in 9 European countries. The
Lancet. http//dx.doi.org/a0.1016/S0140-6738(13)62631-8 February 26, 2014.

Gaining Prescription Drug Insurance Reduced Inpatient Medicare Payments
MedicalResearch.com Interview with: Prof. Robert Kaestner
University of Illinois at Chicago – Institute of Government and Public Affairs Chicago, IL 60607 and
National Bureau of Economic Research New York, NY 10016-4309
• Prof. Kaestner: Gaining prescription drug insurance through Medicare Part D was associated
with a 8% reduction in the probability of a hospital admission, a 7% reduction in Medicare
payments for inpatient services per person (who obtained insurance), and a 12% reduction in
hospital resource use per person.
MedicalResearch.com: What should clinicians and patients take away from your report?
• Prof. Kaestner: Prescription drugs are, on average, a substitute for inpatient care.
The greater use of prescription drugs that comes with insurance prevents hospitalizations.
MedicalResearch.com What recommendations do you have for future research as a result
of this study?
• Prof. Kaestner: Future research should try to identify the specific biological and clinical
mechanisms underlying the finding that prescription drug use decreased hospitalization.
• Citation:
Kaestner, Robert and Long, Cuiping and Alexander, G. Caleb, Effects of Prescription Drug
Insurance on Hospitalization and Mortality: Evidence from Medicare Part D (February 2014).
NBER Working Paper No. w19948. Available at SSRN: http://ssrn.com/abstract=2403672

After Outgrowing One Food Allergy, Some Patients Develop Second Allergic Reaction to Same Food
MedicalResearch.com Interview with: Jonathan M. Spergel, M.D., Ph.D.
The Children’s Hospital of Philadelphia Chief, Allergy Section
Associate Professor of Pediatrics
Perelman School of Medicine at the University of Pennsylvania
• Dr. Spergel: We were examining patients with Eosinophilic Esophagitis, an unique food allergy of
the esophagus. We found a subset of patients, who in the past had IgE mediated reaction to the
food (hives, anaphylaxis) and had outgrown it. Two-three years after outgrowing the food, then the
patients developed Eosinophilic Esophagitis to the same food.
• Dr. Spergel: Yes, this finding indicated two important things:
• You can get two different reactions to the same food.
• The mechanism of the reactions for IgE-mediated reactions and Eosinophilic Esophagitis are
different.
• Dr. Spergel: For patients and clinician, if someone has outgrown the food allergy. But, then gets
new symptoms, it could be the food that they had outgrown.
• MedicalResearch.com: What recommendations do you have for future research as a result of this
study?
• Dr. Spergel: This research raises two important questions.
• How often does this happen? How many patients that outgrown their food allergy will develop a
different reaction to the same food?
• Is there a better to treat patients with Eosinophilc Esophagitis or food allergy due to this difference
in mechanism?
• Citation:
• Maggadottir et al, “Development of Eosinophilic Esophagitis to Food after Development of IgE
Tolerance to the Same Food, abstract 990, presented March 2, 2014 at the AAAAI Annual Meeting.

Pneumonia Risk Increased From Sleep Apnea
Dr. Vincent Yi-Fong Su
Department of Chest Medicine Taipei Veterans General Hospital Taipei, Taiwan
• Answer: We found interestingly that patients with sleep apnea experienced a 1.20-fold (95% CI,
1.10-1.31; p <0.001) increase in incident pneumonia compared to patients without sleep apnea. We
also demonstrated an “exposure-response relationship,” in that the patients with more severe
sleep apnea might have a higher risk for pneumonia than did those of milder severity.
MedicalResearch.com: What should clinicians and patients take away from your report?
• Answer: Based on our results, primary care generalists are suggested to survey sleep disorders
among pneumonia patients without other identified risk factors or among patients with recurrent
pneumonia. For sleep specialists, our finding may broaden the spectrum of sleep apnea-related
complications, which may not limited to the cardiovascular or neurocognitive aspects. As well,
while caring CPAP users, every effort should be made to minimize the risk of pneumonia, such as
enhanced cleaning of CPAP tubing and humidifier or being vigilant if recurrent pneumonia was
noted among CPAP users.
study?
• Answer: Future more elaborate prospective research is needed to confirm our finding and elucidate
the possible underlying mechanisms.
• Citation:
• Sleep apnea and risk of pneumonia: a nationwide population-based study
• Vincent Yi-Fong Su, Chia-Jen Liu, Hsin-Kai Wang, Li-An Wu, Shi-Chuan Chang,Diahn-Warng Perng,
Wei-Juin Su,Yuh-Min Chen, Elizabeth Ya-Hsuan Lin ,Tzeng-Ji Chen and Kun-Ta Chou
• CMAJ cmaj.131547; published ahead of print March 3, 2014, doi:10.1503/cmaj.131547

Chronic Urticaria: Supplemental Vitamin D3 for Hives Management
MedicalResearch.com Interview with: Dr. Jill A Poole MD
Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Medicine
College of Medicine, University of Nebraska Medical Center
The Nebraska Medical Center, Omaha, Nebraska
• Dr. Poole: Our study found that adding vitamin D 4000 IU daily to a cocktail of anti-allergy medications resulted in a further
40% reduction in hive symptom scores at 3 months. There was no further reduction in hive symptoms when 600 IU of
vitamin D was added to the anti-allergy medications. The anti-allergy regimen utilized was triple drug therapy with cetirizine
(twice daily), ranitidine (twice daily), and montelukast (once daily). No adverse reactions occurred.
Dr. Poole: Were any of the findings unexpected?
• Dr. Poole: Clinicians and patients might want to consider adding 4000 IU of vitamin D with their anti-allergy medications to
gain further reduction in hive symptoms. They should note that supplemental vitamin D should be taken for 3 months.
Vitamin D has a long half life, meaning, it takes 6-8 weeks to replenish vitamin D stores and/or reach a steady state. Our
findings of a beneficial role for add-on vitamin D were independent of patient’s vitamin D status; therefore, a minimum of a
3 month trial of supplemental vitamin D might be a consideration for management, even in patients with normal serum
vitamin D levels.
• Dr. Poole: Future research should consider extending the observation time past 3 months, as benefits with vitamin D
supplementation were not at 6 weeks, but at 3 months. It is not known whether further improvement would occur beyond 3
months. Next, our study was a single center study, and a multi-center study could be considered. Next, our study
population was representative of persons in our Mid-West region, and we would recommend studying the effects of
supplemental vitamin D in other diverse and under-represented, minority populations.
• Citation:
• Beneficial role for supplemental vitamin D3 treatment in chronic urticaria: a randomized study
• Annals of Allergy, Asthma & Immunology
• Available online 5 February 2014
Andy Rorie, Whitney S. Goldner, Elizabeth Lyden, Jill A. Poole

Should Dental Extractions Be Done Prior to Heart Surgery?
Dr. Kendra J. Grim
Department of Anesthesiology
Mayo Clinic, Rochester, MN 55905
•
MedicalResearch.com: What are the main findings of the study?
• Dr. Grim: “The current guidelines say that if possible, treating the dental problems that patients have before heart surgery is best, to try
to prevent both early and late heart infections. But the data is very unclear, because it’s very difficult to study. We found in our study
that their risk of serious complications after having teeth removed may be higher than we thought. We were primarily looking at stroke,
heart attack, renal failure and death. We found that actually the incidence of having one of those major morbidities was 8 percent. Of
that 8 percent, we had six patients, or 3 percent, of the total group who died between their dental surgery and scheduled heart
surgery, so these patients never made it to their heart surgery. An additional 3 percent of patients died after heart surgery. “
• Dr. Grim: “Yes. The risk of having a serious complication after tooth extraction before heart surgery was higher than we expected, at
8%. Current ACC/AHA guidelines that rate dental extraction a low-risk procedure (<1% risk of major complication or death) may not
apply to this patient population.”
MedicalResearch.com
Dr. Grim: “Our take-home message is that discussion among the specialists – the cardiologist, cardiac surgery, the oral surgeon and the
anesthesiologist – would be in the best interest of the patient, to try to ascertain the risk for this particular patient. If we think the risk
from taking the teeth out is low, but the benefit is perceived to be high, then we would proceed with the tooth extraction. But if we
think the risk of having the teeth extracted before heart surgery is too high, then we would consider not proceeding with the tooth
extraction. We really feel that it’s important, because the data is unclear, that rather than following a general rule of thumb, physicians
assess each patient’s individual risk.
• Dr. Grim: “Our hope is that this will spark further conversation that will lead to further research. It’s difficult to study, because the
incidence of the infection in the new artificial heart valve is very low. Infection rates have not been studied in patients for bypass grafts,
for the ventricular assist devices, total artificial hearts, and there has been minimal research in heart transplantation. So there are a lot
of additional avenues open for research in this area to better understand the risk/benefit.”
• Citation:
• Morbidity and Mortality Associated With Dental Extraction Before Cardiac Operation
• Mark M. Smith, David W. Barbara, William J. Mauermann, Christopher F. Viozzi, et al
• The Annals of Thoracic Surgery Vol. 97, Issue 3, Pages 838-844

Stroke: Speedier Thrombolysis Therapy Prolongs Disability-Free Life
MedicalResearch.com Interview with: Atte Meretoja, MD, PhD, MSc (Stroke Medicine)
Associate Professor and Principal Fellow (Neurology), University of Melbourne
The Royal Melbourne Hospital Australia
Associate Professor of Neurology, University of Helsinki Helsinki University Central Hospital, Finland
• Dr. Meretoja: We used observational prospective data of consecutive stroke patients (n=2258) treated with intravenous
thrombolysis in Australian and Finnish centers and a pooled analysis of thrombolysis trials to model the shift in patient
outcomes with reducing treatment delays. We found out that each minute the treatment can be delivered faster granted on
average 1.8 days of extra healthy life (95% prediction interval 0.9 to 2.7). In practice, this means that each 15 minute
decrease in treatment delays provides an average equivalent of one month of additional disability-free life.
• Dr. Meretoja: The magnitude of benefit from small realistically achievable gains in streamlining thrombolysis services has
not been quantified before. This study provides a meaningful metric and an impetus to take action.
• Dr. Meretoja: Even small achievements in streamlining acute stroke services provide very large health benefits for the
patient. Co-operation of the ambulance service, ED, and the stroke team is critical, and validated methods for achieving this
have been described by us and others. Best practice centers currently achieve <20 minutes median in-hospital delays, while
most hospitals take more than an hour, effectively losing months of healthy life with every treated patient. Every hospital
should know its door-to-needle times for stroke thrombolysis, take action to reduce these, and monitor the results.
• Dr. Meretoja: Intravenous thrombolysis remains the only evidence-based acute recanalization therapy in stroke. Translation
to practice has been slow, with the therapy most often contraindicated due to delays. This research should promote service
streamlining for the benefit of our patients. Future research should concentrate on methods to further reduce delays and
increase rate of use.
• Citation:
• Stroke Thrombolysis Save a Minute, Save a Day
• Atte Meretoja,Mahsa Keshtkaran,Jeffrey L. Saver,Turgut Tatlisumak,Mark W. Parsons,Markku Kaste,Stephen M.
Davis,Geoffrey A. Donnan,and Leonid Churilov
• Stroke. 2014;STROKEAHA.113.002910published online before print March 13 2014, doi:10.1161/STROKEAHA.113.002910

Sports-Related Concussion Diagnosis Using Blood Biomarker Tau
MedicalResearch.com Interview with: Pashtun Shahim, MD
Clinical Neurochemistry Laboratory
Institute of Neuroscience and Physiology Department of Neurochemistry
Sahlgrenska University Hospital, Mölndal
Sweden
• Dr. Shahim: Sports-related concussion in professional ice hockey players is associated with acute
axonal and astroglial injury. Plasma total tau, which is a highly central nervous system-specific
protein, is a promising biomarker to be used both in the diagnosis of concussion and in the
decision-making when an athlete can be declared fit to return to play.
• Dr. Shahim: The levels of total tau correlated with the duration of post-concussive, and the levels
even at 144 h after concussion remained significantly elevated in players with persistent post-
concussive symptoms > 6 days compared with the levels after a friendly game.
• Dr. Shahim: Blood biomarkers, specifically total tau is a promising biomarker to be used in the
diagnosis and prognosis of athletes with sports-related concussion, as well as patients seeking
emergency clinics due to concussion or mild traumatic brain injury.
study?
• Dr. Shahim: These results are from an on going multi center study on professional ice hockey
players from the Swedish Hockey League. These findings need to be replicated in a larger sample
size. The promising results should also be evaluated in relation to general concussion in emergency
care units.
• Citation:
• Blood Biomarkers for Brain Injury in Concussed Professional Ice Hockey Player
• Shahim P, Tegner Y, Wilson DH, et al. Blood Biomarkers for Brain Injury in Concussed Professional Ice
Hockey Players. JAMA Neurol. 2014;():. doi:10.1001/jamaneurol.2014.367.

Ocular Injuries from Laser Pointers
Glenn Yiu, MD, PhD
Duke Ophthalmology
Duke University Medical Center
• Dr. Yiu: This paper reported a child who suffered injury to both eyes from a powerful blue laser pointer purchased via the
internet from overseas. Our report reviews the scientific basis for laser injuries in eyes and the factors that may affect
outcomes, such as power, wavelength, duration, and distance of exposure. Newer green and blue lasers, especially high-
powered ones, may be more prone to inducing eye injuries. We summarized the clinical features of ocular laser injuries,
methods of prevention, and discussed how consumer availability of high powered lasers may require careful federal
regulations.
• Dr. Yiu: In this case, the laser caused retinal hemorrhages in both eyes resulting in severe loss of vision. This is uncommon
since laser injuries over short distances are typically unilateral. The circumstances are unclear surrounding the young victim
playing with an adult who directed the laser at him in jest. Fortunately, the hemorrhages resolved after several months and
did not appear to result in permanent damage. This is not always the case, as some patients may suffer permanent scarring
or recurrent bleeding from abnormal growth of blood vessels (known as choroidal neovascularization) as a result of the laser
damage.
• Dr. Yiu: Unlike trained personnel in occupational settings, the average consumer may not be familiar with laser safety
practices. Ocular laser injuries among consumers may be underreported, and prompt referral to an ophthalmologist is
necessary for diagnosis, possible treatment, and documentation for medicolegal purposes. Laser goggles are important for
prevention of laser injuries, and care should be taken to ensure that the laser goggles are specific for the wavelength of the
laser being used.
• Dr. Yiu: Increased available of lasers in the consumer market requires careful regulation. High powered devices, particularly
those with shorter-wavelengths, should be clearly labeled and safety instructions provided to ensure use of appropriate
laser safety goggles or other barriers. Improved consumer awareness will be important for preventing future incidents from
occurring.
• Citation: Ocular Safety of Recreational Lasers
• JAMA Ophthalmol. 2014 Jan 9. doi: 10.1001/jamaophthalmol.2013.5647. [Epub ahead of print]
• Yiu G, Itty S, Toth CA.

CABG Surgery in Patients with Acute Coronary Syndromes and Chronic Kidney Disease
Martin Holzmann, MD, PhD
Department of Emergency Medicine, Karolinska University Hospital
Stockholm Sweden.
• Dr. Holzmann: The main finding is that patients with renal dysfunction are at increased risk of
cardiovascular events after undergoing CABG for acute coronary syndromes.
• Dr. Holzmann: We would have expected that the association would have been stronger than it was. We
found an association only in patients with severe renal dysfunction.
• Dr. Holzmann: Cardiologists should not hesitate to send their patients with renal dysfunction to undergo
CABG in case it is needed. The prognosis after CABG is excellent even in patients with rather advanced
renal dysfunction.
• Dr. Holzmann: More research is needed to elucidate if there is a causal association between renal
dysfunction and cardiovascular outcomes. Maybe renal dysfunction is merely a marker of increased risk or
a composite of other cardiovascular risk factors.
• Citation:
• Long‐term Cardiovascular Outcomes in Patients With Chronic Kidney Disease Undergoing Coronary Artery
Bypass Graft Surgery for Acute Coronary Syndromes
• Citation:
• Long‐term Cardiovascular Outcomes in Patients With Chronic Kidney Disease Undergoing Coronary Artery
Bypass Graft Surgery for Acute Coronary Syndromes
• Martin Holzmann, Tomas Jernberg, Karolina Szummer, and Ulrik Sartipy
• J Am Heart Assoc. 2014;3:e000707, originally published March 4, 2014, doi:10.1161/JAHA.113.000707

Surgical Safety Checklists Did Not Substantially Improve Surgical Outcomes
MedicalResearch.com Interview with: David R. Urbach, M.D
From the Institute for Clinical Evaluative Sciences Department of Surgery
Institute of Health Policy, Management and EvaluationUniversity of Toronto, the University Health Network
Toronto, ON M5G 2C4, Canada
• Dr. Urbach: After surgical safety checklists were adopted by hospitals in Ontario, surgical
outcomes—death after surgery, complications, length of stay, readmissions—did not improve
substantially.
• Dr. Urbach: These findings were unexpected because previous research suggested that there were
large benefits from introducing surgical safety checklists. For example, the risk of death after
surgery was reduced between 30% and 50% among early studies.
• Dr. Urbach: Improving surgical safety requires more than just introducing safety checklists.
Meaningful improvements in safety will probably require comprehensive, team-based interventions
that result in a lasting change in culture.
study?
• Dr. Urbach: We need to continue to explore how safety and quality can be improved in surgery.
Checklists are an important part of this, but not sufficient by themselves to cause major
improvements.
• Citation:
• Introduction of Surgical Safety Checklists in Ontario, Canada
• David R. Urbach, M.D., Anand Govindarajan, M.D., Refik Saskin, M.Sc., Andrew S. Wilton, M.Sc., and
Nancy N. Baxter, M.D., Ph.D.
• N Engl J Med 2014; 370:1029-1038
• March 13, 2014DOI: 10.1056/NEJMsa1308261

Bipolar Disorder: Genome-Wide Association Study
MedicalResearch.com Interview with: Prof. Dr. Sven Cichon, PhD
Director, Division of Medical Genetics University Hospital Basel
Human Genomics Research Group Department of Biomedicine
University of Basel Basel, Switzerland
• MedicalResearch.com Interview with:
Prof. Dr. Sven Cichon, PhD
Director, Division of Medical Genetics
University Hospital Basel
Human Genomics Research Group
Department of Biomedicine
University of Basel Basel, Switzerland
• MedicalResearch.com: What were the main findings of the study?
• Answer: We have identified two new gene regions that represent pieces of the jigsaw puzzle of genetic and non-genetic factors that lead to the
development of bipolar disorder. One is the gene ADCY2 (Adenylate Cyclase 2) which is involved in signal transmission within nerve cells. The other
region comprises two genes, both presumably playing a role in neurodevelopmental processes (MIR2113 and POU3F2). Importantly, these results
come out of the largest of these kinds of studies so far, involving altogether more than 24,000 people.
MedicalResearch.com: Were the findings unexpected?
• Answer: The exact nature of the identified genes and their involvement in bipolar disorder is new to us. We have indication from other susceptibility
genes found in previous studies of bipolar disorder that both nerve cell signalling as well as neurodevelopmental processes may play a role in this
common neuropsychiatric disorder. However, there are literally thousands of genes that are somehow related to these biological functions in the
human brain. Our study now support the importance of these biological functions in disease development and specify more of the involved genes.
• Answer: The most important message is that these kinds of studies help to understand the biological foundations of bipolar disorder. It is a long way
because the disease is so complex, but step by step we are getting there. Biological knowledge of the disease will eventually be the starting point for
new therapies.
• Answer: The recent successes in identifying genetic factors involved in bipolar disorder and other complex diseases are the result of large
international collaborations. In the present study, we have joined data generated by the MooDS consortium –involving researchers from Europe,
Australia, and Canada- and the largest international consortium in the field of psychiatric genetic research, the Psychiatric Genomics Consortium
(PGC). This enabled us to assemble the most powerful data set to date for such a systematic genetic study. Large numbers are necessary to clearly
see the minor genetic differences of individual genes between patients and controls against the ‘background noise’ of genetic differences.
• It is therefore of utmost importance to continue and extend large, international collaborations involving numerous psychiatrists, geneticists and
statisticians world-wide.
• Citation:
• Genome-wide association study reveals two new risk loci for bipolar disorder
• Nature Communications 5, Article number:3339 doi:10.1038/ncomms4339

Long-Term Risk of Stroke Raised by PreHypertension
Dingli Xu, MD
From Department of Cardiology
Nanfang Hospital, Southern Medical University, Guangzhou, China
• Answer：Our study showed that after controlling for multiple cardiovascular risk factors, the blood
pressure range at 120-139/80-89 mm Hg (defined as ‘prehypertension’ in JNC 7), is significant
associated with long-term risk of stroke. The results were consistent across stroke type, stroke
endpoint, age, study characteristics, follow-up duration, and ethnicity. More importantly, even low-
range prehypertension (BP 120-129/80-84mmHg) increased the risk of stroke compared with
optimal BP (<120/80 mm Hg), and the risk was higher in individuals with high-range
prehypertension (BP 130-139/85-85mmHg). In particular, we found that compared with individuals
with optimal blood pressure individuals with low-range prehypertension were 44% more likely to
develop stroke, and this risk was even greater (95%) in individuals with high-range prehypertension.
•
• Answer: Yes, we believed that two findings are very interesting. First, prehypertension, which
seemed “normal” in the past, is significant associated with risk of stroke, even after adjusted
multiple cardiovascular risk factors. This means that the mild elevation of blood pressure could
directly increases the risk of stroke.
• Second, even low range prehypertension, which is defined as ‘normal blood pressure’ in some
hypertension guideline, could also increase the risk of stroke significantly. This result is different
with prior studies and meta analysis. Therefore, our findings reaffirms the importance of the
definition of “prehypertension” rather than being “normal”.

Long-Term Risk of Stroke Raised by PreHypertension
Dingli Xu, MD
From Department of Cardiology
Nanfang Hospital, Southern Medical University, Guangzhou, China
• Answer: These findings have important clinical and public health implications. First, clinicians and patients should be aware
of that blood pressure range at 120-139/80-89mmHg is not “normal”. These individuals are at a high risk to progress to
sustained hypertension, as well as CVD, especially stroke, so periodic screening is important. Second, considering the robust
evidence of an association between prehypertension and the risk of stroke shown in our study, it is preferable to consider
earlier interventions for prehypertension among the general population. Currently, lifestyle modification is the mainstay of
treatment for prehypertension in the general population (e.g. quit smoking, increased physical activity, maintain proper body
weight.). This should be recommended to every individuals with prehypertension.
• However, because of the significant difference in the risk of stroke for BP between 120–129/80–84 mm Hg and 130–139/85–
89 mm Hg, we suggest that, for clinicians, this category should be subdivided into low- and high-range prehypertension.
Further studies are needed to reveal better predictors of high-risk subpopulations with prehypertension (especially in high-
range prehypertension) to select subpopulations for future controlled trials of pharmacological treatment.
• Answer: In our study, we found that prehypertension, even in the low range, elevates the risk of stroke after adjusting for
multiple cardiovascular risk factors. However, whether treatment of prehypertension can reduces the risk of target organ
damage is still with controversies. Based on the lack of prospective, randomized trials examining the effects of anti-
hypertensive therapy on reducing target organ damage specifically in prehypertensives, professional societies do not
recommend drug treatment in prehypertension, even in high-range prehypertension.
• So we think that there is a great gap to be covered between epidemiological studies and randomized controlled studies in
prehypertension. Prehypertensive individuals are at a high risk to progress to sustained hypertension, as well as CVD,
especially stroke. So for therapeutic implications, we emphasize that lifestyle intervention, but not medical intervention is
the mainstay of treatment for prehypertension. However, high-risk subpopulations with prehypertension are needed to be
selected for future controlled trials of pharmacological treatment.
• Citation:
• Prehypertension and the risk of stroke A meta-analysis
• Yuli Huang, MD, Xiaoyan Cai, MD, Yingying Li, MD, Liang Su, MD, Weiyi Mai, MD, PhD, Sheng Wang, MD, Yunzhao Hu, MD,
Yanxian Wu, MD and Dingli Xu, MD
• Published online before print March 12, 2014, doi: 10.1212/WNL.0000000000000268 Neurology

Low Birth Weight Babies at Higher Risk of Infertility Later in Life
MedicalResearch.com Interview with: Dr Josefin Vikström
Division of Obstetrics and Gynecology
Department of Clinical and Experimental Medicine
Faculty of Health Sciences Linköping University, Linköping, Sweden
• Dr. Vikström: Our study showed that women with a female infertility factor were more than two
times more likely to have been born with a low birth weight (less than 2500g) or small for
gestational age compared to women where the cause of infertility was unknown and/or male.
• Dr. Vikström: We hypothesized that being born with a low birth weight (<2500g) would increase
the risk of infertility since the risk of other diseases such as cardiovascular disease and the
metabolic syndrome is increased in these individuals. However, since this study is the first of its
kind it was difficult to predict the results.
• Dr. Vikström: Women born with a low birth weight might be at increased risk of infertility later on
in life but more studies are needed to verify these results.
study?
• Dr. Vikström: More studies are needed to determine that there is an association between low birth
weight and infertility in women and in that case why these women are at increased risk of
infertility.
• Citation:
• Birth characteristics in a clinical sample of women seeking infertility treatment: a case–control
study
• Josefin Vikström, Mats Hammar, Ann Josefsson, Marie Bladh, Gunilla Sydsjö
• BMJ Open 2014;4:3 e004197 doi:10.1136/bmjopen-2013-004197

Sleep Decreased In Children Who Watch Excessive Television
MedicalResearch.com Interview with: Marcella Marinelli, MSc, PhD
Center for Research in Environmental Epidemiology
Hospital del Mar Research Institute
Spanish Consortium for Research on Epidemiology and Public Health Barcelona, Spain
• MedicalResearch.com: What are the main findings of your study?
• Answer: We found that each hour a day of television viewing decreased
sleep by 13 % in the Joint group. I also examined the changes in
terms of television behavior: Children who increased
television exposure at 4 years in Sabadell and Valencia reduced sleep
duration of a 20%. While children who reduced the amount of time spent
in front of the television had some recovery of sleep duration.
• Also children who watched more or exactly 1.5 hours of television
at 2 years in Sabadell and Valencia reduced their sleep duration of a
30% compared to children who watched television for less than 1.5 hours
per day. Moreover children that change their behavior and at 4 years
reduced the amount of time spent in front of television (in this case
children who pass from the >=1.5 hours per day group to the <1.5 hours
per day group) had a recovery effect, increasing their sleep duration,
although the coefficient is not statistically significant. Also
children who pass from watching television for less than 1.5 hours per
day and increase the amount of time spent in front of the television
(more or equal to 1.5 hours per day) at 4 years decrease their sleep
duration of 30%.
• Answer: Yes I could not believe that some of the children in my study watch television for 6-8 hours per day!
• Answer: Clinicians should recommend parents to limit the use of television and
other devices. Parents should avoid continuous exposure of children in
front of the television and mobile phones and stimulate them with other
activities such as music, sport or family life. Also play together
will be beneficial. Television should be limited to no more than an
hour and also the content of TV program should be monitored. There are
some studies that evaluated the relationship between TV viewing
and aggressive behavior. So be careful!
• Answer: Future research should consider the type of programs that children
watch and other television habits in a longitudinal design. We could
not distinguish between active and passive television exposure (TV is
just switched on for example) so should be also interesting to
evaluate if there is any differences on sleep duration. It will also
important to evaluate more assessments for television and
sleep during the all week.
• I would like to add that I am very active in divulgating
epidemiological research based on children in my life and for this
reason I have created a blog for parents in Italy
www.bambinofelice.it.
• Citation:
• Marinelli M, Sunyer J, Alvarez-Pedrerol M, et al. Hours of Television Viewing and Sleep Duration in Children: A Multicenter Birth Cohort Study. JAMA Pediatr. 2014;():.
doi:10.1001/jamapediatrics.2013.3861.

Randomized Controlled Trials: 25% Discontinued, Mostly in Patient Studies
Matthias Briel, MD, MSc
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
• Dr. Briel: Using a retrospective cohort of 1017 randomized controlled trials (RCTs) based on archived protocols approved by six research
ethics committees in Switzerland, Germany, and Canada between 2000 and 2003, we found that 25% of initiated RCTs were
discontinued. While discontinuation was common with RCTs involving patients (28%), it was rare in RCTs with healthy volunteers (3%).
The most commonly reported reason for RCT discontinuation was poor recruitment (10% of included RCTs). We found that trials with
investigator sponsor (versus industry) and those with smaller planned sample sizes were at higher risk of discontinuation due to poor
recruitment. Of discontinued RCTs, up to 60% remained unpublished. Trial investigators rarely informed research ethics committees
about trial discontinuation and publication.
• Dr. Briel: We did not expect such a poor reporting to ethics committees. Overall, only 96 of 253 discontinuations (38%) were reported
to research ethics committees. For randomized controlled trials discontinued due to poor recruitment discontinuation was reported in
24 of 101 RCTs (24%), for RCTs discontinued due to futility it was 16 of 37 RCTs (43%), and for RCTs discontinued due to harm it was 13
of 24 RCTs (54%).
• MedicalResearch.com: What should clinical researchers and patients take away from your report?
• Dr. Briel: Our findings indicate that ethical obligations of RCTs are frequently not met. Failure to report premature discontinuation to
ethics committees limits the ethics committees’ ability to carry out their mandate of ensuring ethical trial conduct and to monitor
problematic randomized controlled trials. Not sharing with the scientific community the challenges resulting in RCT discontinuation
removes any opportunity for learning within the trialist community, including identifying risks and instituting preventative action. Non-
publication of inconclusive results leads to loss of valid evidence that could contribute to systematic reviews and meta-analyses. Our
findings also highlight the necessity of current efforts to enhance the transparency, quality, and accessibility of trial protocols and
results such as the ‘Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)’ and ‘AllTrials’ (www.alltrials.net)
initiatives. Patient recruitment to trials should be closely monitored and contingency plans should be in place if it is lower than
expected.
• Dr. Briel: For investigator-initiated RCTs, stakeholders including trial investigators, funding agencies, and ethics committees need to
develop strategies to prevent trial discontinuation. Based on our data retrospective or prospective screening of patients appears to hold
little promise in estimating recruitment rates, but conducting a pilot study including patients’ consent to check that recruitment
strategies are adequate might be effective. Further research is necessary to determine the optimal length of pilot trials and to develop
reliable prediction models for recruitment performance.
• Citation:
• Prevalence, Characteristics, and Publication of Discontinued Randomized Trials
• Kasenda B, von Elm E, You J, et al. Prevalence, Characteristics, and Publication of Discontinued Randomized Trials. JAMA.
2014;311(10):1045-1052. doi:10.1001/jama.2014.1361.

E-Cigarettes Use By Adolescents May Lead to Heavier Smoking
MedicalResearch.com Interview with: Lauren Dutra, ScD
Postdoctoral Scholar, UCSF School of Medicine
Cardiovascular Research Institute
San Francisco, CA 94143
• Answer: Middle and high school students who used e-cigarettes were more likely to smoke tobacco
cigarettes. They were also more likely to progress from experimenting with tobacco cigarettes to
becoming regular smokers.
• Teen smokers who used e-cigarettes were more likely to be planning to quit in the next year and less likely
to have abstained from smoking recently, compared to smokers who had never used e-cigarettes. They
were also more likely to be heavier smokers (smoke more cigarettes per day) than those who had never
tried e-cigarettes.
• Answer: E-cigarettes are unlikely to be effective cessation aids for adolescents and may encourage
cigarette smoking among adolescents.
• Answer: Longitudinal research is needed to determine the precise role that e-cigarettes play in initiation
to nicotine and precisely what fraction of kids start with e-cigarettes and progress to smoking cigarettes
(and vice versa). The fractions of kids who use e-cigarettes who have never smoked (20% in middle school
and 7% in high school) are the minimums for the rate of nicotine use among kids with e-cigs.
• Citation:
• Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents: A Cross-sectional Study
• Lauren M. Dutra ScD, Stanton A. Glantz PhD
• JAMA Pediatr. 2014;168(7):1-9. doi:10.1001/jamapediatrics.2013.5488

Massachusetts Health Care Reform and the Working Poor
Liane J. Tinsley, MPH Associate Research Scientist
Department of Epidemiology New England Research Institutes, Inc.
Watertown, MA 02472
• Answer: For this study, we analyzed health insurance data from a cohort of community-dwelling individuals between the
ages of 30-79 at baseline, in Boston, MA. Massachusetts health care reform legislation, including the expansion of Medicaid,
resulted in substantial overall gains in coverage in our study population. Despite being targeted by the law, the working poor
(those currently working for pay, either part- or full-time and earning less than 200% of the US federal poverty threshold for
household size) continued to report lower rates of insurance coverage following reform (13.3% without insurance),
compared to the both non-working poor (4.7% without insurance) and the not poor (5.0% without insurance).
• Answer: Gains in insurance coverage among the working poor came overwhelmingly via public channels (e.g. Medicaid),
while less than half of working poor reported private insurance coverage following reform. This was despite the fact that one
of the main goals of the law was to tie private insurance coverage to employment (such as the employer mandate to provide
health benefits to fulltime employees). This aspect of the law does not appear to have provided substantial benefits to the
working poor in this study population. This may be related to occupational differences among subgroups: many of the
study’s participants reported working in service or construction and repair occupations, jobs which are often part-time or
seasonal in nature, and to which the employer mandate may not apply.
• Answer: Despite overall gains in insurance coverage following healthcare reform, disparities persisted among the working
poor, who represent a growing sector of the U.S. population.
• Answer: Our findings may have implications for the 2014 rollout of the federal Patient Protection and Affordable Care Act
(ACA), which is modeled on the MA health reform experiment. We believe our findings may be relevant for predicting the
potential future success of the ACA among similar populations.
• Citation:
• Has Massachusetts health care reform worked for the working poor? Results from an analysis of opportunity
Liane J. Tinsley, MPH Susan A. Hall, PhD, John B. McKinlay, PhD
Annals of Epidemiology Volume 24, Issue 4, April 2014, Pages 312–318

PTSD and Plasma Marker of Inflammation CRP
Dr. Dewleen Baker MD
Veterans Affairs (VA) San Diego Healthcare System, San Diego, California
• Dr. Baker: The main finding of this study is that a marker of peripheral inflammation, plasma CRP may be
prospectively associated with PTSD symptom emergence, suggesting that inflammation may predispose to
PTSD.
• Dr. Baker: While these were new findings, they had been hypothesized, and were therefore not totally
unexpected.
• Dr. Baker: Implications for clinicians are that:
• 1) In their patients with PTSD, they should be on the alert for physical co-morbidities known to be
associated with inflammation, such as metabolic syndrome, cardiovascular disease, and arthritis in their
patients with PTSD. Reduction in inflammation in those patients may help prevent these secondary
physical conditions that are more frequent in PTSD patients.
• Moreover, in light of the findings in the paper by Eraly et al., lowering inflammation may be a good
strategy for primary prevention of PTSD in individuals exposed to extreme stress.
• Dr. Baker: It will be important to replicate these findings. If they are replicated, the next step will be to
better understand the causal relationships between psychiatric disorders and inflammation, which are
likely to be complex. A better understanding may lead to better interventions and/or treatments, and may
also help us understand the observed relationship between PTSD and co-occurring medical disorders, such
as metabolic syndrome, heart disease and allergies/arthritis.
• Citation
• Assessment of Plasma C-Reactive Protein as a Biomarker of PTSD
• Eraly SA, Nievergelt CM, Maihofer AX, et al. Assessment of Plasma C-Reactive Protein as a Biomarker of
Posttraumatic Stress Disorder Risk. JAMA Psychiatry. 2014;():. doi:10.1001/jamapsychiatry.2013.4374.

Depression and Hearing Impairment in Adults
MedicalResearch.com Interview with: Dr. Chuan-Ming Li MD, PhD
Statistician (Health/Medicine)
Division of Scientific Programs
The National Institute on Deafness and Other Communication Disorders
• Dr. Chuan-Ming Li: We used data on adults 18 years or older from the National Health and Nutrition
Examination Survey for the study and found that prevalence of moderate to severe depression was 4.9
percent for individuals who reported excellent hearing, 7.1 percent for those with good hearing and 11.4
percent for participants who reported having a little hearing trouble or greater hearing impairment (HI).
Depression rates were higher in women than in men. The prevalence of depression increased as hearing
impairment became worse, except among participants who were deaf. There was no association between
self-reported HI and depression among people ages 70 years and older; however, an association between
moderate HI measured by pure-tone threshold hearing exams and depression was found in women aged
70 years and older but not in men.
• Dr. Chuan-Ming Li: We did not find a significant relationship between depression and self-
reported hearing impairment among male or female adults aged 70 years and older. Rather, we found a
significant association between depression and a threshold-based measure of “moderate” HI, defined as
better ear pure tone average between 35 and 50 dB hearing level, among females. These apparently
inconsistent results may reflect the tendency of people in different age groups to assess their HI
differently. For example, older people may be less likely to self-report HI activity limitations compared with
younger people.
• In the present study, the prevalence of depression increased as hearing difficulty became greater, i.e.,
from “excellent” hearing to “a lot of trouble” but decreased among those who self-reported as “deaf”. The
strongest association was for those with moderate trouble hearing. One reason for this result may be that
people with severe to profound hearing impairment have had a different experience in their exposure and
access to hearing health care. They are much more likely to have been ‘discovered’ and encouraged to try
rehabilitation (hearing aids, alternative listening devices, cochlear implants, etc.). Thus, their lower
prevalence of depression may be because a higher proportion of them have had access to hearing health
care services and thereby have obtained more help and earlier interventions than those with mild to
moderate hearing impairment.

Depression and Hearing Impairment in Adults
MedicalResearch.com Interview with: Dr. Chuan-Ming Li MD, PhD
Statistician (Health/Medicine)
Division of Scientific Programs
The National Institute on Deafness and Other Communication Disorders
• Dr. Chuan-Ming Li: People with any hearing impairment should access health care professional
services and be willing to try rehabilitation (e.g. hearing aids, alternative listening devices, etc) if
recommended. Health care professionals should be aware of increased risk of depression among
adults with hearing loss and may be better able to improve the quality of life among people with
hearing impairment by recognizing signs and symptoms of depression and referring patients for
mental health services.
study?
• Dr. Chuan-Ming Li: Because of the cross-sectional nature of the survey, we cannot determine
whether hearing impairment predates depression or to what extent self-reported depression may
impact self-perceived hearing impairment.
• According to WHO reports, depression ranks as the number 1 highest burden among chronic
diseases and adult-onset hearing loss is likely number 2 (next highest burden) in ‘developed’
countries such as the US, Canada, Australia, Western Europe, etc. The “cause and effect”
relationship between HI and depression is unknown. A longitudinal/prospective study may be
needed. Further study is needed to find reasons why women suffer more depression than men.
• Citation:
• Hearing Impairment Associated With Depression in US Adults, National Health and Nutrition
Examination Survey 2005-2010
• Li C, Zhang X, Hoffman HJ, Cotch M, Themann CL, Wilson M. Hearing Impairment Associated With
Depression in US Adults, National Health and Nutrition Examination Survey 2005-2010. JAMA
Otolaryngol Head Neck Surg. 2014;():. doi:10.1001/jamaoto.2014.42.

Alcohol in Early Pregnancy Associated with Preterm, Small Babies
Camilla Nykjaer, PhD Student
School of Food Science and Nutrition
University of Leeds, Leeds, UK
• Answer: In our study, there was an association between the mother drinking alcohol during early pregnancy and being born
preterm or small for gestational age. Babies of women who drank more than 2 units of alcohol per week in the first
trimester were more likely to be born preterm, small for gestational age and with lower birth weight compared to non-
drinkers, even after adjusting for a range of confounders including cotinine levels as a biomarker for smoking status. The
association with preterm birth was present even in those mothers who reported drinking less than 2 units/week.
• Answer: Alcohol is a known teratogen. Evidence regarding the damaging effects of heavy drinking in pregnancy is well
established, the effect of low intakes is however unclear. We believe our study adds evidence that even very low intakes of
alcohol in early pregnancy can have adverse effects on birth outcomes. Maternal alcohol intakes which exceeded 2
units/week in the period leading up to pregnancy were also found to be associated with fetal growth, suggesting that the
peri-conceptual period may be particularly sensitive to the effects of alcohol on the fetus.
• Answer: Clinicians should advise pregnant women and women planning to become pregnant to avoid drinking alcohol all
together when trying to conceive and throughout pregnancy.
• Answer: This is an observational study so conclusions about causality cannot be drawn. Due to ethical reasons a randomised
controlled trial cannot be conducted but it would be important to reproduce this study in other cohorts with bigger sample
sizes in different countries.,
• Citation:
• Maternal alcohol intake prior to and during pregnancy and risk of adverse birth outcomes: evidence from a British
cohortCamilla Nykjaer,Nisreen A Alwan,Darren C Greenwood,Nigel A B Simpson,Alastair W M Hay, Kay L M White, Janet E
Cade
• J Epidemiol Community Health jech-2013-202934Published Online First: 10 March 2014 doi:10.1136/jech-2013-202934

ALS Amyotrophic Lateral Sclerosis: FDG-PET as Marker of Cerebral Involvement
MedicalResearch.com Interview with: Prof. Dr. Philip Van Damme, MD, PhD
Neuromuscular Reference Center, Neurology Department, University Hospitals Leuven
Vesalius Research Center, VIB, Leuven
Leuven Institute of Neurodegenerative Disorders (LIND)
KU Leuven, Belgium
• Prof: Van Damme: Earlier FDG-PET studies carried out in the 80’ties already pointed out that patients with
ALS had decrease glucose uptake in the brain that is more extended than the motor cortex, at least at the
group level. Of course, this imaging technique has been improved since then.
• We prospectively assessed the diagnostic and prognostic value of FDG-PET in patients that were referred
to us because a diagnosis of ALS was suspected.
• The most important finding of our study probably is that FDG-PET shows perirolandic and variable
frontotemporal hypometabolism in most patients with ALS at the first presentation in our clinic. It suggests
that FDG-PET is a very sensitive marker of cerebral involvement in ALS, which has a high sensitivity at the
single patient level.
• In addition our study revealed that the co-occurrence of extensive prefrontal or anterior temporal
hypometabolism was present in about 10% of patients and had a negative effect on survival after disease
onset.
• Prof: Van Damme: Given the earlier studies with FDG-PET in ALS, we expected to find hypometabolism at
the patient group level. However, the sensitivity of the abnormalities seen at the single patient level was
quite unexpected.
• Also, to find extensive regions of hypometabolism in the prefrontal and/or anterior temporal lobes in
patients with ALS were you wouldn’t expect the co-occurrence of frontomporal dementia at first sight in
about 10% of patients was remarkable. The detection of frontotemporal involvement becomes more and
more important because it has consequences for the prognosis and management of the patients. FDG-PET
may become an important ancillary test to look for frontotemporal involvement in patients with ALS, even
if no cognitive or behavioral problems are reported by the patient and his or her family.

ALS Amyotrophic Lateral Sclerosis: FDG-PET as Marker of Cerebral Involvement
MedicalResearch.com Interview with: Prof. Dr. Philip Van Damme, MD, PhD
Neuromuscular Reference Center, Neurology Department, University Hospitals Leuven
Vesalius Research Center, VIB, Leuven
Leuven Institute of Neurodegenerative Disorders (LIND)
KU Leuven, Belgium
• Prof: Van Damme: There is an unmet need for an imaging biomarker of disease in ALS, both from
the diagnostic as well as from the prognostic point of view. FDG-PET may play its role herein, but
further studies are needed to confirm this.
study?
• Prof: Van Damme: Our results suggest that FDG-PET has diagnostic and prognostic value at the
single patient level in ALS, but several questions remain unanswered. How specific is the finding of
perirolandic and frontotemporal hypometabolism in ALS? It seems to be a very sensitive marker in
patients with ALS, but we don’t know its specificity or its discriminative value for ALS mimic
syndromes.
• MedicalResearch.com: How good is the correlation between FDG-PET findings and
neuropsychological scores?
• Prof: Van Damme: How early in the disease course do these changes appear? In our study we
scanned the patients when they first presented at our center, but we don’t know if these changes
are already present in earlier disease stages or even in the presymptomatic stage.
• Citation:
• Value of 18Fluorodeoxyglucose–Positron-Emission Tomography in Amyotrophic Lateral Sclerosis: A
Prospective Study
• Van Laere K, Vanhee A, Verschueren J, et al. Value of 18Fluorodeoxyglucose–Positron-Emission
Tomography in Amyotrophic Lateral Sclerosis: A Prospective Study. JAMA Neurol. 2014;():.
doi:10.1001/jamaneurol.2014.62.

Orthopedic Trauma Patients: ‘Doctor Shopping’ and Increased Narcotics Use
Brent J. Morris, M.D.
Shoulder and Elbow Surgery Fellowship
Texas Orthopaedic Hospital in affiliation with the University of Texas Houston Health Science Center, Houston, Texas
• Dr. Morris: There are concerns that an increasing percentage of patients are receiving narcotics by “doctor shopping” or
seeking narcotics from multiple providers. One in five of our postoperative orthopedic trauma patients received narcotics
from one or more additional providers other than the treating surgeon.
• Patients that doctor-shopped postoperatively had a significant increase in narcotic prescriptions, duration of narcotics, and
morphine equivalent dose per day.
• Dr. Morris: The prevalence of postoperative doctor shopping was surprising, and unfortunately, this number likely
underestimates the true extent of postoperative doctor shopping.
• Dr. Morris: This study highlights the importance of counseling our patients in the postoperative period about narcotic use.
The treating surgeon is responsible for pain control in the immediate postoperative period, and additional narcotics should
not be sought from multiple providers without alerting the treating surgeon. Pain control in the postoperative period is very
important, especially in patients with traumatic injuries; however, there needs to be better awareness among patients and
providers to ensure that patients do not engage in doctor shopping.
• Dr. Morris: We now recognize that a high percentage of patients doctor shop postoperatively and research should be
focused on combating postoperative doctor shopping and quantifying the impact of narcotic use on clinical outcomes and
patient satisfaction.
• Citation:
• The American Academy of Orthopaedic Surgeons Meeting 2014
Narcotic Use and Postoperative Doctor Shopping in the Orthopaedic Trauma

Emergency Room Visits for Insulin-Related Hypoglycemia
Andrew I. Geller, MD
Medical Officer in the Division of Healthcare Quality Promotion at CDC.
• Dr. Geller: Using CDC’s national medication safety monitoring system, we estimated that, each year,
there were about 100,000 visits made to U.S. emergency departments (EDs) for insulin-related
hypoglycemia and errors during 2007-2011, or about half a million ED visits over the 5-year study
period. This is important because many of these ED visits for insulin-related hypoglycemia may be
preventable.
• We also found these ED visits were more common with increasing age: every year, 1 in 49 insulin-
treated seniors (aged 65 years or older) visited the ED because of hypoglycemia while on insulin or
because of a medication error related to insulin. Among the very elderly (aged 80 years or older),
this number was 1 in 8 annually.
For cases where a medication error was involved, we found the number one contributing factor to
the ED visit was a meal-related problem, such as a patient skipping a meal after taking a rapid-
acting insulin or not adjusting their insulin doses when their food intake was reduced.
• The second most common contributing factor to ED visits where medication errors were involved
was mix-up between insulin products. Typically, this involved patients who intended to take a long-
acting insulin (such as insulin glargine or insulin detemir), but instead took a rapid-acting insulin
(such as insulin aspart or insulin lispro).
• Dr. Geller: Insulin is a complicated drug to manage; we expected that it would cause many ED visits
for adverse events. But we did not appreciate the full severity of these insulin-related ED visits. For
example, almost two-thirds of emergency department visits involved hypoglycemia with either loss
of consciousness, confusion, or injury (e.g., falling after fainting) and almost one-third of patients
had to be hospitalized. Another marker of the severity of these cases was that over 50% involved
very low blood glucose (50 mg/dL or lower).

Emergency Room Visits for Insulin-Related Hypoglycemia
Andrew I. Geller, MD
Medical Officer in the Division of Healthcare Quality Promotion at CDC.
• Dr. Geller: It is important that patients on insulin and other diabetes medicines continue their medications. What our
findings point to is an opportunity to improve how these patients can safely use their insulin. For example, we know that
planning meals around dosing of certain types of insulin (e.g., rapid-acting insulin products) is one of the most important
things that patients can do to prevent hypoglycemia. . Additionally, many patients take not just one type of insulin, but two
or even three. For such patients, it is important that they pay close attention to which insulin products they are
administering so as to prevent confusion or mix-up’s among products. It is also important for patients to recognize the signs
and symptoms of hypoglycemia, educate their families and caregivers on recognizing hypoglycemia, and be ready to
promptly treat hypoglycemia (with glucose tablets or orange juice, for example).
• Clinicians are well acquainted with the risks of insulin for individual patients, but may not fully appreciate the public health
burden of ED visits and hospitalizations from insulin-related hypoglycemia and errors. Until very recently, clinical guidelines
emphasized the long-term benefits of blood glucose control through tight blood glucose control. This study supports more
recent clinical guidance for the need to balance the short-term risks of tight blood glucose control with the potential long-
term benefits. This includes taking into account an individual’s risk for hypoglycemia based on such factors as age, other
chronic conditions, and their ability to safely manage insulin.
• Dr. Geller: We recommend ongoing national public health surveillance to continue to follow trends in ED visits and
hospitalizations for insulin-related hypoglycemia and errors, and to measure the impact of changing diabetes treatment
guidelines and hypoglycemia prevention efforts. Future research could focus on additional specific risk factors that
contribute to serious insulin-related hypoglycemia, such as types of insulin products involved, levels of glycemic control, and
patient’s comorbidities. Moving forward, it will be important to identify best practices for preventing these types of
events, including emphasizing importance of meal-planning and avoiding product mix-up’s in diabetes self-management
education, as well as improving packaging of the various insulin products (pens, vials) so that they are more easily
distinguished.
• Citation:
• National Estimates of Insulin-Related Hypoglycemia and Errors Leading to Emergency Department Visits and
Hospitalizations
• Geller AI, Shehab N, Lovegrove MC, et al. National Estimates of Insulin-Related Hypoglycemia and Errors Leading to
Emergency Department Visits and Hospitalizations. JAMA Intern Med. 2014;():. doi:10.1001/jamainternmed.2014.136.

Suicide in Children and Adolescents: Relationship Between Peer Victimization, Cyberbullying
Mitch van Geel, PhD
Institute of Education and Child Studies, Leiden University
Leiden, the Netherlands
• Dr.van Geel: We performed a meta-analysis, which is a way to statistically summarize effect sizes from earlier studies.
Individual studies often provide varying effect sizes, which makes it difficult to judge whether and how strong variables are
related. Furthermore, study characteristics (sampling methods, response rates, controlling for certain confounders) might
influence study results. By using a meta-analysis it can be analyzed to what extent study characteristics are related to results;
if a particular result only tends to be established in studies with certain designs (for example a convenience sample), we
might wonder whether such an effect really exists; but if we find that a particular outcome is unrelated to study
characteristics or found in studies with relatively stronger designs, we might feel more certain in concluding that a relation
between variables (bullying-suicide thoughts or attempts) exists.
• By using a meta-analysis we established a significant relation between bullying and thoughts about suicide, and bullying and
suicide attempts, and we found that these results were unrelated to study characteristics.
• Dr.van Geel: Mostly the result that cyberbullying as more strongly related to suicide thoughts than traditional bullying. This
may be because victims of cyberbullying feel denigrated for a wider evidence, or because the event is stored on the internet,
they may relive denigrating experiences more often.
• Dr.van Geel: Suicide is one of the most important causes of adolescent mortality; in the United States, between 5 to 8
percent of adolescents will attempt suicide within a year. We found that attempted suicides are significantly related to
bullying, a highly prevalent behavior among adolescents, of which estimates suggest that between 15-20 percent of
adolescents is involved as a bully, as a victim, or as both. This further stresses the need to reduce bullying and help the
victims of bullying.
Dr.van Geel: Studies should continue to further establish how cyberbullying affects children and adolescents, but even more
importantly, we should continue to study how both traditional and cyberbullying can be reduced.
• Citation:
• van Geel M, Vedder P, Tanilon J. Relationship Between Peer Victimization, Cyberbullying, and Suicide in Children and
Adolescents: A Meta-analysis. JAMA Pediatr. 2014;():. doi:10.1001/jamapediatrics.2013.4143.

Excessive Substance Use: Training Family Physicians to Deliver Brief Intervention
Dr. Dagmar Haller, MD, PhD
Médecin adjointe agrégée Unité Santé Jeunes
Hôpitaux Universitaires de Genève Suisse
• MedicalResearch.com Interview with:
Dr. Dagmar Haller, MD, PhD
Médecin adjointe agrégée
Unité Santé Jeunes
Hôpitaux Universitaires de Genève Suisse
• Dr. Haller: One year after a consultation with a family doctor there was a 28% reduction in the proportion of excessive
substance users among those who had reported excessive use at the start of the study but there was no significant
difference between the group that received counseling and the one that did not.
• Dr. Haller: The natural history of substance use in adolescence is that of an increase with age. Thus the important reduction
in the proportion of excessive substance users at follow-up, particularly in the control group, was unexpected.
• Dr. Haller: Consultations by family physicians have the potential to influence adolescent substance use trajectories, but the
best way to exert this influence remains unknown.
• Dr. Haller: Future research should explore the potential role of multisectoral collaborations, including the interaction
between a disapproving community environment and interventions in the clinical setting. More research is also needed on
the best models for effective screening of substance use in young people attending family practices.
• Citation:
• Effectiveness of training family physicians to deliver a brief intervention to address excessive substance abuse among young
patients
• Dagmar M. Haller, Anne Meynard, Daniele Lefebvre, Obioha C. Ukoumunne, Françoise Narring, and Barbara Broers
• CMAJ cmaj.131301; published ahead of print March 10, 2014, doi:10.1503/cmaj.131301

COPD: Using FEV6 to Identify More Affected Patients
Surya P Bhatt MD Assistant Professor
Division of Pulmonary and Critical Care Medicine
University of Alabama at Birmingham
• Dr. Bhatt: The forced vital capacity (FVC) maneuver is a difficult maneuver for many patients and the
forced expiratory volume in the first 6 seconds (FEV6) has been shown to be a reliable substitute. We used
imaging findings on computed tomography, COPD questionnaires and tests of exercise capacity to
compare these two spirometric measures (FEV1/FVC and FEV/FEV6) in the diagnosis of airflow obstruction,
and showed that FEV6 can be reliably substituted for FVC. Our findings suggest that using FEV6 may in fact
identify more patients with disease than by using FVC.
• Dr. Bhatt: We expected FEV6 to be a good substitute for FVC. The finding that using FEV6 may in fact
identify patients with more respiratory morbidity was unexpected.
• Dr. Bhatt: FEV1/FEV6 can be reliably substituted for FEV1/FVC in the diagnosis of airflow obstruction. The
FEV6 measurement is easier both for patients and for pulmonary function laboratory personnel.
• Dr. Bhatt: These findings should be tested in a real world scenario where quality control is not as rigorous
as in a clinical trial setting. We expect FEV6 to be even more reliable when quality control is not very
stringent.
• Citation:
• FEV1/FEV6 to Diagnose Airflow Obstruction: Comparisons with Computed Tomography and Morbidity
Indices
• Bhatt SP1, Kim YI, Wells JM, Bailey WC, Ramsdell JW, Foreman MG, Jensen RL, Stinson DS, Wilson CG, Lynch
DA, Make BJ, Dransfield MT; the COPDGene Investigators.
• Ann Am Thorac Soc. 2014 Jan 22. [Epub ahead of print]

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